tbuckley/cabot-search huggingface dataset:
Metabolic side effects in persons with schizophrenia during mid‐ to long‐term treatment with antipsychotics: a network meta‐analysis of randomized controlled trials
Authors: Angelika Burschinski, Johannes Schneider‐Thoma, Virginia Chiocchia, Kristina Schestag, Dongfang Wang, Spyridon Siafis, Irene Bighelli, Hui Wu, Wulf‐Peter Hansen, Josef Priller, John M. Davis, Georgia Salanti, Stefan Leucht
Journal: World Psychiatry (2023)

Metabolic side effects of antipsychotic drugs can have serious health consequences and may increase mortality. Although persons with schizophrenia often take these drugs for a long time, their mid‐ to long‐term metabolic effects have been studied little so far. This study aimed to evaluate the mid‐ to long‐term metabolic side effects of 31 antipsychotics in persons with schizophrenia by applying a random‐effects Bayesian network meta‐analysis. We searched the Cochrane Schizophrenia Group's Study‐Based Register of Trials (up to April 27, 2020) and PubMed (up to June 14, 2021). We included published and unpublished, open and blinded randomized controlled trials with a study duration &gt;13 weeks which compared any antipsychotic in any form of administration with another antipsychotic or with placebo in participants diagnosed with schizophrenia. The primary outcome was weight gain measured in kilograms. Secondary outcomes included “number of participants with weight gain”, fasting glucose, total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, and triglycerides. We identified 137 eligible trials (with 35,007 participants) on 31 antipsychotics, with a median follow‐up of 45 weeks. Chlorpromazine produced the most weight gain (mean difference to placebo: 5.13 kg, 95% credible interval, CrI: 1.98 to 8.30), followed by clozapine (4.21 kg, 95% CrI: 3.03 to 5.42), olanzapine (3.82 kg, 95% CrI: 3.15 to 4.50), and zotepine (3.87 kg, 95% CrI: 2.14 to 5.58). The findings did not substantially change in sensitivity and network meta‐regression analyses, although enriched design, drug company sponsorship, and the use of observed case instead of intention‐to‐treat data modified the mean difference in weight gain to some extent. Antipsychotics with more weight gain were often also among the drugs with worse outcome in fasting glucose and lipid parameters. The confidence in the evidence ranged from low to moderate. In conclusion, antipsychotic drugs differ in their propensity to induce metabolic side effects in mid‐ to long‐term treatment. Given that schizophrenia is often a chronic disorder, these findings should be given more consideration than short‐term data in drug choice.
The future of psychopharmacology: a critical appraisal of ongoing phase 2/3 trials, and of some current trends aiming to de‐risk trial programmes of novel agents
Authors: Christoph U. Correll, Marco Solmi, Samuele Cortese, Maurizio Fava, Mikkel Højlund, Helena C. Kraemer, Roger S. McIntyre, Daniel S. Pine, Lon S. Schneider, John M. Kane
Journal: World Psychiatry (2023)

Despite considerable progress in pharmacotherapy over the past seven decades, many mental disorders remain insufficiently treated. This situation is in part due to the limited knowledge of the pathophysiology of these disorders and the lack of biological markers to stratify and individualize patient selection, but also to a still restricted number of mechanisms of action being targeted in monotherapy or combination/augmentation treatment, as well as to a variety of challenges threatening the successful development and testing of new drugs. In this paper, we first provide an overview of the most promising drugs with innovative mechanisms of action that are undergoing phase 2 or 3 testing for schizophrenia, bipolar disorder, major depressive disorder, anxiety and trauma‐related disorders, substance use disorders, and dementia. Promising repurposing of established medications for new psychiatric indications, as well as variations in the modulation of dopamine, noradrenaline and serotonin receptor functioning, are also considered. We then critically discuss the clinical trial parameters that need to be considered in depth when developing and testing new pharmacological agents for the treatment of mental disorders. Hurdles and perils threatening success of new drug development and testing include inadequacy and imprecision of inclusion/exclusion criteria and ratings, sub‐optimally suited clinical trial participants, multiple factors contributing to a large/increasing placebo effect, and problems with statistical analyses. This information should be considered in order to de‐risk trial programmes of novel agents or known agents for novel psychiatric indications, increasing their chances of success.
The alliance in mental health care: conceptualization, evidence and clinical applications
Authors: Bruce E. Wampold, Christoph Flückiger
Journal: World Psychiatry (2023)

The concept of alliance reflects the collaborative relationship between a clinician and a patient, defined as consisting of three elements: a) the agreement on the goals of treatment; b) the agreement on a task or series of tasks; c) the development of a bond. Although much of the theory and research on the alliance comes from the domain of psychotherapy, the concept is applicable to any practice involving a person seeking help and a socially sanctioned healer. An extensive research evidence suggests that the alliance (typically measured at the third or fourth session) is a robust predictor of the outcomes of various forms of psychotherapy, even when prior symptom improvement and other factors are considered. Both the clinician and the patient bring to the therapy situation different capacities to form an alliance. Factors concerning the patient include, among others, the diagnosis, attachment history and style, motivation, and needs for affiliation. However, the benefits of the alliance have been found to be mostly due to the therapist's contribution, in particular his/her facilitative interpersonal skills, including verbal fluency, communication of hope and positive expectations, persuasiveness, emotional expression; warmth, acceptance and understanding; empathy, and alliance rupture-repair responsiveness. Placebo studies have allowed to experimentally manipulate aspects of the relationship between a therapist and a patient in non-psychotherapy contexts. In these settings, two components of the relationship have emerged: an emotional one (involving being cared for and understood by the clinician) and a cognitive one (including the belief in the competence of the therapist to select and administer an effective treatment). Here we propose a model that describes three pathways through which the alliance creates benefits, named CARE (caring, attentive, real and empathic), EXPECTANCY, and SPECIFIC. Although research and clinical attention have mostly focused on the alliance between a clinician and a patient in face-to-face interactions, there is preliminary evidence concerning the alliance between patients and other clinic staff, systems of care, or the program in Internet-mediated services. These new research areas clearly require further development.
Combination Chemotherapy and Whole Liver Irradiation for Hepatic Tumors
Authors: Michael A. Friedman
Journal: Liver Cancer (1985)

This chapter is a selected review of attempts to combine chemotherapy with conventional beam, external, whole liver irradiation. The special individual aspects of radiation and chemotherapy are presented in chapters 10–18 and will not be reiterated here. Each modality is somewhat effective but none is totally sufficient, so combining them has been attempted. This chapter reviews the published efforts to treat patients with liver cancers utilizing simultaneous radiation and chemotherapy.
The association between atopic dermatitis, cognitive function and school performance in children and young adults
Authors: Ida Vittrup, Yuki M F Andersen, Lone Skov, Jashin J Wu, Tove Agner, Simon F   Thomsen, Alexander Egeberg, Jacob P Thyssen
Journal: British Journal of Dermatology (2022)

Children with atopic dermatitis (AD) may have disturbed sleep, affected self-esteem and decreased quality of life, likely interfering with performance in school.To examine the association between hospital-managed paediatric AD, school performance and cognitive function.In this cross-sectional study we linked data from the Danish national registers and identified three populations between 2001 and 2019. Population 1 comprised children with graduation grades registered from lower secondary school, population 2 comprised adolescents with registration of an upper secondary graduation mean, and population 3 comprised male conscripts with registration of an IQ test score. AD was defined as a hospital diagnostic code (inpatient or outpatient) prior to the exam or conscription date, and was stratified according to severity, activity and atopic comorbidity. Outcomes included graduation mean from lower and upper secondary school, special educational assistance in primary and lower secondary school, and IQ at conscription.In total, 770 611 (12 137 with AD), 394 193 (6261 with AD) and 366 182 (4539 with AD) children and adolescents were included in populations 1 (lower secondary graduation), 2 (upper secondary graduation) and 3 (conscription), respectively. In lower secondary school, children with severe AD had significantly lower overall, written and oral graduation grade means compared with children with mild AD: respectively, difference -0.29 [95% confidence interval (CI) -0.45 to -0.13, P < 0.001], difference -0.26 (95% CI -0.42 to -0.10, P = 0.0016) and difference -0.30 (95% CI -0.49 to -0.11, P = 0.0018). In upper secondary school, adolescents with AD performed similarly to their peers without AD. Young men with AD scored significantly lower IQ test means at conscription examination than male conscripts without AD: difference -0.60 (95% CI -0.87 to -0.32, P < 0.001).AD, in particular when severe, is associated with lower school performance in childhood and IQ in young men, which can interfere with academic achievements in life. Optimization of treatment of children with AD and specific educational support to children with severe AD could be needed.
Efficacy and tolerability of pharmacological treatments for insomnia in adults: A systematic review and network meta-analysis
Authors: Jing-Li Yue, Xiang-Wen Chang, Jun-Wei Zheng, Le Shi, Ya-Jie Xiang, Jian-Yu Que, Kai Yuan, Jia-Hui Deng, Teng Teng, Yang-Yang Li, Wei Sun, Hong-Qiang Sun, Michael V. Vitiello, Xiang-Dong Tang, Xin-Yu Zhou, Yan-Ping Bao, Jie Shi, Lin Lu
Journal: Sleep Medicine Reviews (2023)
Single-cell RNA sequencing identifies precise tolerogenic cellular and molecular pathways induced by depigmented-polymerized grass pollen allergen extract
Authors: Janice A. Layhadi, Raquel Moya, Tiak Ju Tan, Madison M. Lenormand, Hanisah Sharif, Rebecca V. Parkin, Gemma Vila-Nadal, Oleksandra Fedina, Rongfei Zhu, Wannada Laisuan, Stephen R. Durham, Jerónimo Carnés, Mohamed H. Shamji
Journal: Journal of Allergy and Clinical Immunology (2023)

Background Immunological mechanism of action of allergoids remains poorly understood. Previous models of allergenicity and immunogenicity have yielded sub-optimal knowledge of these immunotherapeutic vaccine products. Novel single-cell RNA-seq technology offers a bridge to this gap in knowledge. Objective To identify the underpinning tolerogenic molecular and cellular mechanisms of depigmented-polymerized Phleum pratense extract. Methods The molecular mechanisms underlying native Phleum pratense (Phl p), depigmented Phl p (DPG-Phl p), and depigmented-polymerized (DPG-POL-Phl p) allergoid were investigated using scRNA-seq. Allergen-specific Th2A, Tfh and IL-10+ Breg cells were quantified by flow cytometry in PBMCs from 16 grass pollen allergics (GPA) and 8 non-atopic controls (NAC). The ability of Phl p, DPG-Phl p and DPG-POL-Phl p to elicit FcεRI and FcεRII-mediated IgE responses was measured by basophil activation test and IgE-FAB assay. Results ScRNA-seq analysis revealed that DPG-POL-Phl p downregulated genes associated with Th2 signaling, induced functional Tregs exhibiting immunosuppressive roles through CD52 and Siglec-10, modulated genes encoding immunoproteasome that dysregulate the processing and presentation of antigens to T cells and promoted a shift from IgE towards an IgA1 and IgG responses. In GPA, DPG-POL-Phl p exhibited reduced capacity to elicit proliferation of Th2A, IL-4+ Tfh and IL-21+ Tfh cells whilst being the most prominent at inducing CD19+CD5hiIL-10+ and CD19+CD5hiCD38intCD24intIL-10+ Breg cell subsets compared to Phl p (all, P<.05). Furthermore, DPG-POL-Phl p demonstrated a hypoallergenic profile through basophil activation and histamine release compared to Phl p (31.54-fold, P<.001). Conclusions ScRNA-seq provides an in-depth resolution of the mechanisms underlying the tolerogenic profile of DPG-POL-Phl p.
Environmental and genetic associations with aberrant early-life gut microbial maturation in childhood asthma
Authors: Yih-Chieh Chen, Yulu Chen, Jessica Lasky-Su, Rachel S. Kelly, Jakob Stokholm, Hans Bisgaard, Klaus Bønnelykke, Casper-Emil Tingskov Pedersen, Bo Chawes, Nancy Laranjo, Scott T. Weiss, Augusto A. Litonjua, Kathleen Lee-Sarwar
Journal: Journal of Allergy and Clinical Immunology (2023)

BackgroundEnvironmental, genetic, and microbial factors are independently associated with childhood asthma.ObjectiveWe sought to determine the roles of environmental exposures and 17q12-21 locus genotype in the maturation of the early-life microbiome in childhood asthma.MethodsWe analyzed fecal 16s rRNA sequencing at age 3 to 6 months and age 1 year to characterize microbial maturation of offspring of participants in the Vitamin D Antenatal Reduction Trial. We determined associations of microbial maturation and environmental exposures in the mediation of asthma risk at age 3 years. We examined 17q12-21 genotype and microbial maturation associations with asthma risk in Vitamin D Antenatal Reduction Trial and the replication cohort Copenhagen Prospective Studies on Childhood Asthma 2010.ResultsAccelerated fecal microbial maturation at age 3 to 6 months and delayed maturation at age 1 year were associated with asthma (P < .001). Fecal Bacteroides was reduced at age 3 to 6 months in association with subsequent asthma (P = .006) and among subjects with lower microbial maturation at age 1 year (q = 0.009). Sixty-one percent of the association between breast-feeding and asthma was mediated by microbial maturation at age 3 to 6 months. Microbial maturation and 17q12-21 genotypes exhibited independent, additive effects on childhood asthma risk.ConclusionsThe intestinal microbiome and its maturation mediates associations between environmental exposures including breast-feeding and asthma. The intestinal microbiome and 17q12-21 genotype appear to exert additive and independent effects on childhood asthma risk.
Extrafibrillarly Demineralized Dentin Matrix for Bone Regeneration
Authors: Xiaoyi Wu, Wenan Peng, Gufeng Liu, Shilei Wang, Bo Duan, Jian Yu, Hongye Yang, Cui Huang
Journal: Advanced Healthcare Materials (2023)

Abstract Dentin is a natural extracellular matrix, but its availability in bone grafting and tissue engineering applications is underestimated due to a lack of proper treatment. In this study, the concept of extrafibrillar demineralization is introduced into the construction of dentin‐derived biomaterials for bone regeneration for the first time. Calcium chelating agents with large molecular weights are used to selectively remove the extrafibrillar apatite minerals without disturbing the intrafibrillar minerals within dentin collagen, resulting in the formation of an extrafibrillarly demineralized dentin matrix (EDM). EDM with distinctive nanotopography and bone‐like mechanical properties is found to significantly promote cell adhesion, migration, and osteogenic differentiation in vitro while enhancing in vivo bone healing of rat calvarial defects. The outstanding osteogenic performance of EDM is further confirmed to be related to the activation of the focal adhesion–cytoskeleton–nucleus mechanotransduction axis. Overall, this study shows that extrafibrillar demineralization of dentin has great potential to produce hierarchical collagen‐based scaffolds for bone regeneration, and this facile top‐down fabrication method brings about new ideas for the biomedical application of naturally derived bioactive materials.
Smart delivery systems for microbial biofilm therapy: Dissecting design, drug release and toxicological features
Authors: A. Sousa, A. Ngoc Phung, N. Škalko-Basnet, S. Obuobi
Journal: Journal of Controlled Release (2023)

Bacterial biofilms are highly protected surface attached communities of bacteria that typically cause chronic infections. To address their recalcitrance to antibiotics and minimise side effects of current therapies, smart drug carriers are being explored as promising platforms for antimicrobials. Herein, we briefly summarize recent efforts and considerations that have been applied in the design of these smart carriers. We guide readers on a journey on how they can leverage the inherent biofilm microenvironment, external stimuli, or combine both types of stimuli in a predictable manner. The specific carrier features that are responsible for their 'on-demand' properties are detailed and their impact on antibiofilm property are further discussed. Moreover, an analysis on the impact of such features on drug release profiles is provided. Since nanotechnology represents a significant slice of the drug delivery pie, some insights on the potential toxicity are also depicted. We hope that this review inspires researchers to use their knowledge and creativity to design responsive systems that can eradicate biofilm infections.
Cognitive behavior therapy vs. control conditions, other psychotherapies, pharmacotherapies and combined treatment for depression: a comprehensive meta‐analysis including 409 trials with 52,702 patients
Authors: Pim Cuijpers, Clara Miguel, Mathias Harrer, Constantin Yves Plessen, Marketa Ciharova, David Ebert, Eirini Karyotaki
Journal: World Psychiatry (2023)

Cognitive behavior therapy (CBT) is by far the most examined type of psychological treatment for depression and is recommended in most treatment guide­lines. However, no recent meta‐analysis has integrated the results of randomized trials examining its effects, and its efficacy in comparison with other psychotherapies, pharmacotherapies and combined treatment for depression remains uncertain. We searched PubMed, PsycINFO, Embase and the Cochrane Library to identify studies on CBT, and separated included trials into several subsets to conduct random‐effects meta‐analyses. We included 409 trials (518 comparisons) with 52,702 patients, thus conducting the largest meta‐analysis ever of a specific type of psychotherapy for a mental disorder. The quality of the trials was found to have increased significantly over time (with increasing numbers of trials with low risk of bias, less waitlist control groups, and larger sample sizes). CBT had moderate to large effects compared to control conditions such as care as usual and waitlist (g=0.79; 95% CI: 0.70‐0.89), which remained similar in sensitivity analyses and were still significant at 6‐12 month follow‐up. There was no reduction of the effect size of CBT according to the publication year (&lt;2001 vs. 2001‐2010 vs. &gt;2011). CBT was significantly more effective than other psychotherapies, but the difference was small (g=0.06; 95% CI: 0‐0.12) and became non‐significant in most sensitivity analyses. The effects of CBT did not differ significantly from those of pharmacotherapies at the short term, but were significantly larger at 6‐12 month follow‐up (g=0.34; 95% CI: 0.09‐0.58), although the number of trials was small, and the difference was not significant in all sensitivity analyses. Combined treatment was more effective than pharmacotherapies alone at the short (g=0.51; 95% CI: 0.19‐0.84) and long term (g=0.32; 95% CI: 0.09‐0.55), but it was not more effective than CBT alone at either time point. CBT was also effective as unguided self‐help intervention (g=0.45; 95% CI: 0.31‐0.60), in institutional settings (g=0.65; 95% CI: 0.21‐1.08), and in children and adolescents (g=0.41; 95% CI: 0.25‐0.57). We can conclude that the efficacy of CBT in depression is documented across different formats, ages, target groups, and settings. However, the superiority of CBT over other psychotherapies for depression does not emerge clearly from this meta‐analysis. CBT appears to be as effective as pharmacotherapies at the short term, but more effective at the longer term.
Corrigendum to “In situ hydrogel capturing nitric oxide microbubbles accelerates the healing of diabetic foot” [Journal of Controlled Release Volume 350 (2022) 93–106]
Authors: Yingzheng Zhao, Lanzi Luo, Lantian Huang, Yingying Zhang, Mengqi Tong, Hanxiao Pan, Jianxun Shangguan, Qing Yao, Shihao Xu, Helin Xu
Journal: Journal of Controlled Release (2023)
A Self‐Reinforcing Nanoplatform for Highly Effective Synergistic Targeted Combinatary Calcium‐Overload and Photodynamic Therapy of Cancer
Authors: Dongdong Guo, Xiaoyong Dai, Kewei Liu, Yuhong Liu, Jiamin Wu, Kun Wang, Shengwei Jiang, Fen Sun, Lijun Wang, Bing Guo, Dongye Yang, Laiqiang Huang
Journal: Advanced Healthcare Materials (2023)

While calcium-overload-mediated therapy (COMT) is a promising but largely untapped therapeutic strategy, combinatory therapy greatly boosts treatment outcomes with integrated merits of different therapies. Herein, a BPQD@CaO2 -PEG-GPC3Ab nanoplatform is formulated by integrating calcium peroxide (CaO2 ) and black phosphorus quantum dot (BPQD, photosensitizer) with active-targeting glypican-3 antibody (GPC3Ab), for combinatory photodynamic therapy (PDT) and COMT in response to acidic pH and near-infrared (NIR) light, wherein CaO2 serves as the reservoir of calcium ions (Ca2+ ) and hydrogen peroxide (H2 O2 ). Navigated by GPC3Ab to tumor cells at acidic pH, the nanoparticle disassembles to CaO2 and BPQD; CaO2 produces COMT Ca2+ and H2 O2 , while H2 O2 makes oxygen (O2 ) to promote PDT; under NIR irradiation BPQD facilitates not only the conversion of O2 to singlet oxygen (1 O2 ) for PDT, but also moderate hyperthermia to accelerate NP dissociation to CaO2 and BPQD, and conversions of CaO2 to Ca2+ and H2 O2 , and H2 O2 to O2 , to enhance both COMT and PDT. After supplementary ionomycin treatment to induce intracellular Ca2+ bursts, the multimodal therapeutics strikingly induce hepatocellular carcinoma apoptosis, likely through the activation of the calpains and caspases 12, 9, and 3, up-regulation of Bax and down-regulation of Bcl-2 proteins. This nanoplatform enables a mutually-amplifying and self-reinforcing synergistic therapy.